During the past year substantial progress has been made in characterizing the adenosine receptor and adenosine uptake site in brain. The major focus has involved the effects of various drugs such as caffeine and carbamazepine on adenosine receptors with results showing that both appear to be antagonists. Ontogenetic and anatomical studies have shown that caffeine obtained thru mothers' milk can modulate the adenosine system in pups and that caffeine has differential effects on adenosine receptor subpopulations. Carbamazepine has been shown to be a competitive inhibitor of the adenosine receptor while having no effect on the adenosine uptake site. The adenosine uptake site has been demonstrated in heart muscle with drugs such as dipyridamole, hexobendine and Dilazep being highly potent inhibitors of binding. We have also completed the autoradiographic localization of adenosine uptake sites in rat brain using [3H]Nitrobenzylthioinosine binding to slide-mounted tissue slices. The dihydropyridine calcium antagonists such as nimodipine and nifedipine are also good inhibitors of binding. Studies with [3H]Nitrendipine binding have also been performed since it is felt that the adenosine receptor may be coupled to the voltage-dependent calcium channel. These studies have thus far defined the binding site and its ontogenetic profile. The adenosine receptor and uptake site are currently being purified utilizing affinity chromatography. These studies are in the preliminary stages of solubilizing both sites and synthesizing an appropriate adenosine analogue coupled resin. Studies are also in progress concerning the effects of alcohol intoxication and withdrawal on adenosine and benzodiazepine receptors. Peripheral type benzodiazepine receptors increase in response to alcohol while central receptors decrease.